In the past, optically active .alpha.-tocopherol (Vitamin E) and derivatives thereof which are the 2R,4'R,8'R isomers of compounds of the formula: ##STR1## have been prepared through isolation from natural sources such as vegetable oil. This procedure suffers from many drawbacks due to the fact that the tocopherol content of these oils is very small. Therefore, a great amount of oil must be processed in order to isolate a small amount of natural alpha-tocopherol. Additionally, the process whereby various tocopherols are isolated from vegetable oil is extremely cumbersome.
Attempts to produce optically active alpha-tocopherol, i.e. 2R,4'R,8'R isomers, synthetically have been difficult because such a compound has three centers of chirality. Optically inactive alpha-tocopherol, i.e. 2RS,4'RS,8'RS isomers, have been prepared and found to be biologically useful, but the biological potency is less than that of the optically active compounds of formula I.
In U.S. Pat. No. 4,113,740 there is disclosed the synthesis of a compound of formula I by coupling a hydroxy protected chromanol aldehyde with a 3R, 7R alkyl phosphonium halide in a Wittig reaction to provide the three centers of chirality in the final product. This is a difficult synthesis in that it requires optically pure fragments chemically resolved in order to introduce three centers of chirality in a compound of formula I.
It has been determined, however, in rat fetal resorption tests that the biological potency of (2R,4'RS,8'RS)-alpha-tocopherol of the formula ##STR2## having only one chiral center, is identical to that of natural Vitamin E, i.e. (2R,4'R,8'R)-.alpha.-tocopherol of formula I which has three centers of chirality.